Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition

Overview

Journal Science

Specialty Science

Date 2013 Feb 2

PMID 23372014

Citations 1304

Authors

Min Yu

Aditya Bardia

Ben S Wittner

Shannon L Stott

Malgorzata E Smas

David T Ting

Steven J Isakoff

Jordan C Ciciliano

Marissa N Wells

Ajay M Shah

Kyle F Concannon

Maria C Donaldson

Lecia V Sequist

Elena Brachtel

Dennis Sgroi

Jose Baselga

Sridhar Ramaswamy

Mehmet Toner

Daniel A Haber

Shyamala Maheswaran

Affiliations

Soon will be listed here.

Abstract

Epithelial-mesenchymal transition (EMT) of adherent epithelial cells to a migratory mesenchymal state has been implicated in tumor metastasis in preclinical models. To investigate its role in human cancer, we characterized EMT in circulating tumor cells (CTCs) from breast cancer patients. Rare primary tumor cells simultaneously expressed mesenchymal and epithelial markers, but mesenchymal cells were highly enriched in CTCs. Serial CTC monitoring in 11 patients suggested an association of mesenchymal CTCs with disease progression. In an index patient, reversible shifts between these cell fates accompanied each cycle of response to therapy and disease progression. Mesenchymal CTCs occurred as both single cells and multicellular clusters, expressing known EMT regulators, including transforming growth factor (TGF)-β pathway components and the FOXC1 transcription factor. These data support a role for EMT in the blood-borne dissemination of human breast cancer.

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